Phase III Study Assessing the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis

C3 Glomerulopathy Clinical Trial

— VALIANT  

Official title:

A Phase 3, Randomized, Placebo-Controlled, Double-Blinded, Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05067127
• Other study ID #: APL2-C3G-310
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 12, 2021
• Est. completion date: December 2024

Study information

• Verified date: March 2024
• Source: Apellis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 3 study to assess the efficacy and safety of twice-weekly subcutaneous (SC) doses of pegcetacoplan compared to placebo in patients with C3 glomerulopathy (C3G) or immune-complex membranoproliferative glomerulonephritis (IC-MPGN) on the basis of a reduction in proteinuria.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

1. Aged at least 18 years; where approved, adolescents (aged 12-17 years) weighing at least 30 kg may also be enrolled.

2. A diagnosis of primary C3G or IC-MPGN (with or without previous renal transplant).

3. Evidence of active renal disease, based on one or more of the following:

1. In adults or adolescents with a baseline renal biopsy (either one collected during screening or a historic biopsy collected within 28 weeks prior to randomization), at least 2+ C3c staining on the baseline renal biopsy.

2. In adolescents not providing a baseline renal biopsy, at least one of the following:

• Plasma sC5b-9 level above the upper limit of normal during screening

• Serum C3 below the LLN during screening

• Presence of an active urine sediment during screening, as evidenced by hematuria with at least 5 red blood cells (RBCs) per high-power field (HPF) and/or red blood cell casts on local or central microscopic analysis of urine.

• Presence of C3 nephritic factor within 6 months of screening, based on central laboratory results or medical history.

4. No more than 50% global glomerulosclerosis or interstitial fibrosis on the baseline biopsy for adult participants or adolescent participants providing a baseline biopsy.

5. At least 1 g/day of proteinuria on a screening 24-hour urine collection and a uPCR of at least 1000 mg/g in at least 2 first-morning spot urine samples collected during screening.

6. eGFR =30 mL/min/1.73 m2 calculated by the Chronic Kidney Disease-Epidemiology Collaboration creatinine equation for adults or the Bedside Schwartz equation for adolescents.

7. Stable regimen for C3G/IC-MPGN treatment, as described below:

1. Angiotensin-converting enzyme inhibitor/, angiotensin receptor blocker, and/or sodium-glucose cotransporter-2 inhibitor therapy that is stable and optimized, in the opinion of the investigator, for at least 12 weeks prior to randomization

2. Stable doses of other medications that can affect proteinuria (eg, steroids, mycophenolate mofetil, and/or other allowed immunosuppressants that the participant is receiving for treatment of C3G or IC-MPGN) for at least 812 weeks prior to the baseline renal biopsy and randomization.

3. If a participant is on prednisone (or other systemic corticosteroid) for C3G or IC-MPGN treatment, the dosage is stable and no higher than 20 mg/day (or equivalent dosage of a corticosteroid other than prednisone) for at least 12 weeks prior to randomization.

8. Have received vaccinations against S pneumoniae, N meningitidis (types A, C, W, Y, and B), and H influenzae (type B) within 5 years prior to randomization or agree to receive vaccinations during screening.

Exclusion Criteria:

1. Previous exposure to pegcetacoplan.

2. C3G/IC-MPGN secondary to another condition (eg, infection, malignancy, monoclonal gammopathy, a systemic autoimmune disease such as systemic lupus erythematosus, chronic antibody-mediated rejection, or a medication), in the opinion of the investigator.

3. Current or prior diagnosis of human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV) infection or positive serology during screening that is indicative of infection with any of these viruses.

4. Body weight greater than 100 kg at screening.

5. Hypersensitivity to pegcetacoplan or to any of the excipients.

6. History of meningococcal disease.

7. Malignancy, except for the following:

1. Cured basal or squamous cell skin cancer

2. Curatively treated in situ disease

3. Malignancy-free and off treatment for =5 years

8. Severe infection (eg, requiring IV antibiotic therapy) within 14 days prior to the first dose of pegcetacoplan.

9. An absolute neutrophil count <1000 cells/mm3 at screening.

10. Use of rituximab, belimumab, or any approved or investigational anticomplement therapy other than pegcetacoplan within 5 half-lives of that product prior to the screening period.

11. Female participants who are pregnant or who are currently breastfeeding and are unwilling to discontinue for the duration of the study and for at least 90 days after the final dose of study drug.

12. Presence or suspicion of severe infection during the screening period (including but not limited to recurrent or chronic infections) that, in the opinion of the investigator, may place the participant at unacceptable risk by study participation.

13. Known or suspected hereditary fructose intolerance.

Related Conditions & MeSH terms

• C3 Glomerulonephritis
• C3 Glomerulopathy
• C3G
• Complement 3 Glomerulopathy
• Complement 3 Glomerulopathy (C3G)
• DDD
• Dense Deposit Disease
• Glomerulonephritis
• Glomerulonephritis, Membranoproliferative
• IC-MPGN
• Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN)
• Membranoproliferative Glomerulonephritis
• Membranoproliferative Glomerulonephritis (MPGN)

Intervention

Drug:
• Pegcetacoplan
Complement (C3) Inhibitor

Other:
• Placebo
Sterile solution of equal volume to active arm

Locations

Country	Name	City	State
Argentina	Hospital Universitario Austral	Buenos Aires
Argentina	Clinica Privada Velez Sarsfield	Córdoba
Argentina	Hospital Privado-Universitario de Cordoba	Córdoba
Australia	Monash University	Box Hill
Australia	St. Vincents Melbourne	Fitzroy
Australia	Canberra Hospital - Renal Clinical Trials & Research Unit	Garran	Australian Capital Territory
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Australia	Princess Alexandra Hospital	Woolloongabba
Austria	Medical University Hospital Innsbruck (43004)	Innsbruck
Austria	Medizinische Universität Wien	Wien
Belgium	Hopital Erasme HUB Service Pharmacie	Bruxelles
Belgium	University Hospital Antwerp (32004)	Edegem
Belgium	Catholic University of Leuven	Leuven
Belgium	CHU Sart-Tilman	Liège
Belgium	Clinical Trials CHU de Liège	Liège
Brazil	Santa Casa de Misericordia de Belo Horizonte	Belo Horizonte	Minas Gerais
Brazil	HC UNESP Botucatu	Botucatu
Brazil	Hospital Universitario Walter Cantidio	Fortaleza
Brazil	Centro de Tratamento de Doencas Renais	Juiz De Fora	Minas Gerais
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre	Porto Alegre	RS
Brazil	Real Hospital Portuguas de Beneficancia em Pernambuco	Recife
Brazil	Hospital das Clinicas de Ribeirao Preto, Division of Nephrology	Ribeirão Preto
Brazil	Nefrologia I-Dor	Rio De Janeiro
Brazil	Ruschel Medicina E Pesquisa Clinica	Rio De Janeiro
Brazil	Hospital de Base	São José Do Rio Preto
Brazil	HCFMUSP-Hospital Clinicas da Faculdade Medicina da Universidade de São Paulo	São Paulo
Brazil	Instituto da Crianca-Hospital das Clinicas University of Sao Paulo	São Paulo
Brazil	UNIFESP - Hospital Sao Paulo	São Paulo
Canada	Hopital Maisonneuve-Rosemont	Montréal	Quebec
Canada	Hospital for Sick Children (11003)	Toronto	Ontario
Czechia	Faculty Hospital Kralovske Vinohrady (42002)	Prague
Czechia	Institute for Clinical and Experimental Medicine	Prague
France	CHU de Bordeaux - Hopital Pellegrin	Bordeaux
France	Hopital Henri-Mondor	Créteil
France	Hospital Edouard Herriot, Hospices Civils de Lyon	Lyon
France	CHU Montpellier, Hopital Lapeyronie	Montpellier
France	Nantes University Hospital	Nantes
France	Hôpital Européen Georges-Pompidou	Paris
France	Hopital Necker (33014)	Paris
France	Lille Regional University Hospital Center, Claude Huriez Hospital, Department of Nephrology	Paris
France	CHU de Saint Etienne, Hospital Nord	Saint-Priest-en-Jarez
France	University Hospital Strasbourg	Strasbourg
France	Rangueil Hospital-University Hospital Center (CHU) of Toulouse	Toulouse
Germany	Charite Universitatsmedizin (49007)	Berlin
Germany	Universitatsklinikum Essen (AoR), Zentrum fur Kinder (49005)	Essen
Germany	Medizinische Hochschule Hannover, Studienzentrum fur Nieren und Hochdruckerkrankungen	Hannover
Germany	Universitatsmedizin Mainz	Mainz
Germany	Universitatsklinikum Munster	Münster
Germany	University Hospital Regensburg (49004)	Regensburg
Israel	Rambam Health Care Campus	Haifa
Israel	Institute of Pediatric Nephrology	Petah Tikva
Italy	Policlinico di Bari	Bari
Italy	Policlinico Sant Orsola-Malpighi	Bologna
Italy	IRCCS Istituto Giannina Gaslini (39012)	Genova
Italy	Universita degli Studi di Messina	Messina
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	Istituto di Ricerche Farmacologiche Mario Negri IRCCS	Milano
Italy	Azienda Ospedaliera Universitaria di Padova (39011)	Padova
Italy	Instituti Clinici Scientifici Maugeri SPA-IRCCS	Pavia
Italy	Ospedale Pediatrico Bambino Gesu	Rome
Japan	Seirei Hamamatsu General Hospital (81004)	Hamamatsu	Shizuoka
Japan	NHO Kanazawa Medical Center	Kanazawa	Ishikawa
Japan	Gunma University Hospital (81006)	Maebashi	Gunma
Japan	Nagasaki University Hospital (81005)	Nagasaki-shi	Nagasaki
Japan	Nagoya University Hospital (81003)	Nagoya-shi	Aichi
Japan	Aichi Children's Health and Medical Center	Obu	Aichi
Japan	Kitano Hospital	Osaka
Japan	Kyorin University Hospital (81009)	Tokyo
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Seoul National University Hospital (82005)	Seoul
Korea, Republic of	Yonsei University College of Medicine, Sinchon Severance Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Soeul
Netherlands	Emma Kinderziekenhuis, Amsterdam UMC	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Radboud University Medical Center	Nijmegen
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Uniwersytecki Szpital Kliniczny Nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi	Lódz
Poland	SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi	Lódz
Spain	Fundació Puigvert	Barcelona
Spain	Hospital Materno Infantil Sant Joan de Deu	Barcelona
Spain	Hospital Universitari Vall D'Hebron	Barcelona
Spain	Hospital Universitario Materno-Infantil Vall d' Hebron, Nefrologia Pediatrica	Barcelona
Spain	Hospital Universitario 12 de Octubre, Nephrology Department	Madrid
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	University Hospital of Virgen del Rocio	Sevilla
Spain	Hospital Universitario Dr Peset	Valencia
Switzerland	Inselspital, Bern University Hospital	Bern
Switzerland	CHUV Lausanne	Lausanne
Switzerland	Universitatsspital Zurich	Zürich
United Kingdom	Gloucestershire Hospitals NHS Foundation Trust	Gloucester
United Kingdom	University Hospitals of Leicester NHS trust (44003)	Leicester
United Kingdom	Evelina London Children Hospital (44016)	London
United Kingdom	Great Ormond Street Hospital Foundation Trust	London
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	Royal Free London NHS Foundation Trust (44015)	London
United Kingdom	St George'Äôs University Hospitals NHS Foundation Trust (44014)	London
United Kingdom	Royal Manchester Children's Hospital	Manchester
United Kingdom	Nottingham Children's Hospital	Nottingham
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Fides Clinical Research, LLC (01042)	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Northeast Clinical Research Center, LLC	Bethlehem	Pennsylvania
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Children's Hospital (01013)	Boston	Massachusetts
United States	Institute for Public Health and Medicine Northwestern University Northwestern University (01041)	Chicago	Illinois
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	MedResearch Inc	El Paso	Texas
United States	Nephrology Associates of Northern IL and Inn (01043)	Fort Wayne	Indiana
United States	University of Florida	Gainesville	Florida
United States	Hackensack Meridian Health	Hackensack	New Jersey
United States	Texas Children's Hospital	Houston	Texas
United States	The University of Iowa	Iowa City	Iowa
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Academic Medical Research Institute	Los Angeles	California
United States	Keck School of Medicine, University of Southern California	Los Angeles	California
United States	Ronald Reagan UCLA Medical Center (01035)	Los Angeles	California
United States	Cohen Children Hospital	New Hyde Park	New York
United States	CUIMC - Columbia Nephrology	New York	New York
United States	NANIU Research Chicago (01040)	Oak Brook	Illinois
United States	UCI Center for Clinical Research	Orange	California
United States	Oregon Health & Science University (01038)	Portland	Oregon
United States	UC Davis Medical Center (Transplant Research) (01016)	Sacramento	California
United States	Renal and Transplant Associates of New England, PC	Springfield	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Apellis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Czechia,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The log-transformed ratio of uPCR at week 26 compared to baseline		Baseline to week 26
Secondary	The proportion of participants who meet the criteria for achieving a composite renal endpoint (a stable or improved eGFR compared to the baseline visit (=15% reduction in eGFR), and a =50% reduction in uPCR compared to the baseline visit.)		Baseline to week 26
Secondary	The proportion of participants with a reduction of at least 50% from baseline in uPCRF		Baseline to week 26
Secondary	Change from baseline in eGFR		Baseline to week 26
Secondary	For participants with evaluable renal biopsies, the change from baseline in the activity score of the C3G histologic index score		Baseline to week 26
Secondary	The proportion of participants with evaluable renal biopsies showing decreases in C3c staining on renal biopsy from baseline		Baseline to week 26